The high affinity IgE receptor Fc epsilonRI is expressed by human intestinal epithelial cells.

Background: IgE antibodies play a paramount role in the pathogenesis of various intestinal disorders. To gain insights in IgE-mediated pathophysiology of the gut, we investigated the expression of the high affinity IgE receptor Fc epsilonRI in human intestinal epithelium.

Methodology/principal Findings: Fc epsilonRI alpha-chain, as detected by immunohistochemistry, was positive in epithelial cells for eight of eleven (8/11) specimens from colon cancer patients and 5/11 patients with inflammation of the enteric mucosa.

Characterization of intrinsic and extrinsic risk factors for celery allergy in immunosenescence.

Recent studies indicated an underestimation of allergies in elderly. In our experimental food allergy model of protein feeding under acid-suppression we aimed to assess whether food allergy can be induced in immunosenescent mice. Furthermore, the impact of gastric digestion on celery allergenicity was evaluated in aged patients.

Incomplete digestion of codfish represents a risk factor for anaphylaxis in patients with allergy.

Background: Fish represents one of the most important allergenic foods causing severe allergic reactions. Nevertheless, it has been shown that gastric digestion significantly reduces its allergenic capacity.

Objective: In this study, we assessed the absorption kinetics of fish proteins and investigated the clinical reactivity of patients with fish allergy to codfish digested at physiological or elevated gastric pH.

Apoptosis-specific activation markers in on- versus off-pump coronary artery bypass graft (CABG) patients.

Background: The relation of epithelial/endothelial apoptosis and secretion of death-inducing receptors (DIR) in comparison to vascular adhesion molecules is not known in patients undergoing the On- versus Off-pump coronary artery bypass graft (CABG) procedure.

Methods: 30 patients were prospectively included in the study (On- vs. Off-pump CABG, each n = 15).

Internal images: human anti-idiotypic Fab antibodies mimic the IgE epitopes of grass pollen allergen Phl p 5a.

Background: The role of anti-idiotypic antibodies in allergic disease is still poorly understood. According to Jerne, anti-idiotypic antibodies to IgE should represent internal images of an allergen. Our aim was to ultimately prove whether this hypothesis holds true in allergy.

Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns.

Toll-like receptors (TLR) represent an ancient front-line defence system that enables the host organism to sense the presence of microbial components within minutes. As inducers of inflammation, TLR act as important triggers of distinct entities such as sepsis or autoimmune disease exacerbation. We report here that vitamin D3 [1alpha,25-dihydroxycholecalciferol, 1,25(OH)(2)D3] suppresses the expression of TLR2 and TLR4 protein and mRNA in human monocytes in a time- and dose-dependent fashion.

Soluble ST2 protein in cardiac surgery: a possible negative feedback loop to prevent uncontrolled inflammatory reactions.

Background: Recent reports have demonstrated that cardiopulmonary bypass (CBP) utilization leads to a TH2 cytokine bias in patients undergoing coronary artery bypass grafting (CABG) operation. The relation of soluble ST2 and secretion of IL-10, markers of TH2 T-cell activation, and IL-13 in relation to immunoglobulin isotope production is not known in patients undergoing On- versus Off-pump (CABG) procedure.

Methods: 30 patients were prospectively included in the study (On- vs Off-pump CABG, each n = 15).

Dimerization of the major birch pollen allergen Bet v 1 is important for its in vivo IgE-cross-linking potential in mice.

In type I allergy, the cross-linking of membrane IgE on B lymphocytes and of cytophilic IgE on effector cells by their respective allergens are key events. For cross-linking two IgE molecules, allergens need at least two epitopes. On large molecules, these could be different epitopes in a multivalent, or identical epitopes in a symmetrical, fashion.

Mimotopes identify conformational epitopes on parvalbumin, the major fish allergen.

Parvalbumin, the major fish allergen, is recognized by allergen-specific IgE of more than 90% of all fish-allergic patients. A detailed knowledge of allergenic structures is crucial for developing a vaccine inducing blocking antibodies specifically directed towards the IgE binding epitopes. In the present study we aimed to use the phage display technique to generate mimotopes, which mimic epitopes on parvalbumin.

Interleukin-1beta-induced prostaglandin E2 production by human gingival fibroblasts is upregulated by glycine.

Background: Human gingival fibroblasts (GFB) may produce prostaglandin E(2) (PGE(2)) in response to proinflammatory cytokines. Elevated concentrations of glycine were previously found in periodontal pockets and saliva of periodontitis patients and, therefore, we aimed to study the influence of glycine on PGE(2) production.

Methods: Human GFB were cultured in the presence of various concentrations of glycine and/or interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-10 and their influence on PGE(2) production was measured.

Targeting antigens to murine and human M-cells with Aleuria aurantia lectin-functionalized microparticles.

Neuraminidases act as a virulence factors for several pathogens that invade the human body through Peyer's patch M-cells. Because of the structural similarity of Aleuria aurantia lectin (AAL) to neuraminidases, we hypothesized that AAL might also target human M-cells. In an in vitro human M-cell co-culture model significantly more particles were transported across the epithelium when microparticles were functionalized with AAL versus those that were not.

Monocyte toll-like receptor 4 expression and LPS-induced cytokine production increase during gestational aging.

Premature newborns are highly susceptible to severe bacterial infections. This is partially due to their immature innate immune system, characterized by decreased neutrophil and monocyte activity as well as by reduced concentrations of complement factors. However, additional mechanisms might be important for innate immunity and are still the subject of considerable debate.

Review of novel particulate antigen delivery systems with special focus on treatment of type I allergy.

For the treatment of infectious diseases, cancer and allergy, the directed induction of an appropriate immune response is the ultimate goal. Therefore, with the development of pure, often very small proteins, peptides or DNA by molecular biology techniques, the research for suitable adjuvants or delivery systems became increasingly important. Particle formulations are made of a variety of materials, including lipids, proteins or amino acids, polysaccharides, polyacrylic substances or organic acids.

Mucosal targeting of allergen-loaded microspheres by Aleuria aurantia lectin.

Murine intestinal M-cells express alpha-L-fucose residues. We constructed alpha-L-fucose-targeting particles for oral immunotherapy of IgE-mediated allergy. Poly(D,L-lactic-co-glycolic acid)-microspheres were loaded with birch pollen allergens, and functionalised with the alpha-L-fucose specific Aleuria aurantia lectin (AAL).

The effects of gastric digestion on codfish allergenicity.

Background: In a recent murine study, we showed that impaired gastric digestion supports the induction of fish allergy by protecting the digestion-sensitive major allergen parvalbumin and thus enhancing its sensitizing properties.

Objective: The aim of the present study was to investigate whether impairment of peptic degradation might also play a role in the effector phase of codfish allergy.

Methods: The resistance of cod proteins to digestion by simulated gastric fluid was assessed in vitro .

Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients.

Recently, we have demonstrated that anti-ulcer drugs, such as H2-receptor blockers and proton pump inhibitors, promote the development of immediate type food allergy toward digestion-labile proteins in mice. The aim of this study was to examine the allergological relevance of these findings in humans. In an observational cohort study, we screened 152 adult patients from a gastroenterological outpatient clinic with negative case histories for atopy or allergy, who were medicated with H2-receptor blockers or proton pump inhibitors for 3 months.

Antiulcer drugs promote oral sensitization and hypersensitivity to hazelnut allergens in BALB/c mice and humans.

Background: Hazelnut allergy can be a consequence of sensitization to cross-reactive pollen, especially from the Fagales family. However, severe allergic reactions after ingestion of hazelnuts without associated pollen allergy have been reported. In these cases, oral sensitization by hazelnut ingestion is plausible.

Affinity determinations of purified IgE and IgG antibodies against the major pollen allergens Phl p 5a and Bet v 1a: discrepancy between IgE and IgG binding strength.

Allergen-specific IgE and IgG antibodies coexist in allergic individuals, but only IgE has anaphylactogenic capacity. This study aimed to determine the association, dissociation and equilibrium constants for the interaction of allergen-specific IgE and IgG with the major grass and birch pollen allergens Phl p 5a and Bet v 1a. We isolated specific IgE and IgG antibodies from pollen allergic patients' sera by a two-step affinity chromatography protocol and controlled the high purity in a recombinant allergen chip microarray.

Isolation and structural analysis of peptide mimotopes for the disialoganglioside GD2, a neuroblastoma tumor antigen.

The disialoganglioside GalAcbeta1-4(NeuAcalpha2-8NeuAcalpha2-3)Galbeta1-4Glcbeta1-1Cer (GD2) is expressed on various tumors, including neuroblastoma, and was defined as a relevant tumor antigen. The monoclonal anti-GD2 antibody 14.18 is widely used for diagnostic purposes in neuroblastoma, and in its mouse/human chimeric form (ch14.

M cell targeting with Aleuria aurantia lectin as a novel approach for oral allergen immunotherapy.

Background: The extent and quality of the immune response to orally applied allergens may critically depend on the precise site of uptake at the intestinal mucosa.

Objective: The aim of this study was to construct allergen vehicles optimized for oral allergen immunotherapy.

Methods: By using a murine model, we examined the immunomodulatory effect of birch pollen proteins entrapped in poly(D,L-lactide-co-glycolide) microspheres, which were specifically targeted to enterocytes or to M cells, in an ongoing T h 2 response.

Mapping of conformational IgE epitopes on Phl p 5a by using mimotopes from a phage display library.

Background: Phl p 5 represents a major allergen of timothy grass pollen (Phleum pratense). Detailed knowledge about the structures responsible for IgE binding would allow the design of a novel generation of allergy vaccines.

Objective: We aimed to characterize the IgE epitopes of Phl p 5a using phage display combined with a molecular modeling approach.

Elevated serum levels of epithelial cell apoptosis-specific cytokeratin 18 neoepitope m30 in critically ill patients.

Apoptosis of the epithelium is deemed to play a pivotal role in the pathogenesis of sepsis. A neoepitope in cytokeratin 18 (CK18), termed M30 neoantigen, becomes available at an early caspase cleavage event during apoptosis of epithelium-derived cells and is not detectable in vital or necrotic epithelial cells. A monoclonal antibody, M30, specifically recognizes a fragment of CK18 cleaved at Asp396 (M30 neoantigen).

Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma.

Objective: T1/ST2, a member of the interleukin (IL)-1 receptor superfamily, is predominantly expressed on type-2 T helper (Th2) cells but not Th1 cells, and plays a role in cell proliferation and Th2 immune response. The relation of soluble ST2, Th1-Th2 cytokine profile, and immunoglobulin (Ig) production in sepsis and trauma patients is not well known.

Design And Setting: Case-control study at a university hospital intensive care unit.

Functionalisation of allergen-loaded microspheres with wheat germ agglutinin for targeting enterocytes.

In this study, we constructed particles applicable for oral immunotherapy of type I allergy by protecting allergens from digestion and supporting intestinal antigen uptake. Therefore, birch-pollen allergens were entrapped in poly(d,l-lactic-co-glycolic acid) microspheres by spray-drying rendering microspheres with a main population of 1-3microm. Microspheres were further coated with wheat germ agglutinin (WGA) to target enterocytes.

Antacid medication inhibits digestion of dietary proteins and causes food allergy: a fish allergy model in BALB/c mice.

Background: Digestible proteins were supposed to be irrelevant for oral sensitization and induction of food allergy. Approximately 10% of the adult population uses antacids for the treatment of dyspeptic disorders, drugs that hinder peptic digestion. In these patients, proteins that are normally degradable might act as food allergens.